New York-based Definium Therapeutics (Nasdaq: DFTX) reported positive topline results from the Phase III Voyage study of DT120 ODT, its proprietary orally disintegrating formulation of lysergide D-tartrate (LSD), in generalized anxiety disorder (GAD), marking the second consecutive Phase III win for the compound in two months. Definium is now on a plausible path toward an NDA submission.
Voyage is a randomized, double-blind, placebo-controlled study that enrolled 214 adults aged 18 to 74 with DSM-5-confirmed GAD and a Hamilton Anxiety Rating Scale (HAM-A) total score of at least 20, across approximately 35 US sites. A single 100 µg dose of DT120 ODT produced a least squares mean HAM-A reduction of 11.6 points at Week 12, versus 6.2 points for placebo — a placebo-adjusted difference of 5.4 points (p<0.0001, Cohen's d=0.81). All multiplicity-controlled secondary endpoints were met, including HAM-A change at Week 1 and Clinical Global Impression-Severity (CGI-S) change at Day 2. Response rates (HAM-A ≥50% reduction) at Week 12 were 43% versus 16% for placebo. Adverse events were mild to moderate, transient, and concentrated on the dosing day; no suicidality signal was observed. The average time to meeting end-of-session checklist criteria was 6.4 hours, with 92% of participants clearing the threshold by hour 8.
LSD is a classic serotonergic psychedelic that acts partly through serotonin 5-HT2A receptor activation. Definium hypothesizes that downstream changes in neuroplasticity contribute to the sustained symptom improvements observed after a single administration, although the precise therapeutic mechanism remains uncertain.
The Voyage result follows the positive Phase III Emerge readout in major depressive disorder (MDD) in June 2026, in which a single DT120 ODT dose produced a placebo-adjusted MADRS reduction of 8.1 points at Week 6 (p<0.0001). The company holds FDA Breakthrough Therapy Designation for DT120 ODT in GAD, which provides a basis for an expedited regulatory dialogue.
A second pivotal GAD study, Panorama, includes an additional 50 µg low-dose arm specifically designed to confound participants' ability to identify their dose condition — a methodological response to the functional unblinding problem inherent to psychedelic trials. Definium said Panorama topline results are expected in September 2026. If Panorama confirms the Voyage signal, Definium would hold two GAD datasets and two MDD datasets.